Diisopropylethylamine → (R)-2-(2-(4-chlorobenzyl)-5-methyl-2H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl)pyrrolidine-1-carboxamide

HRID 2063481노트

반응식

HRID 2063481 반응식
ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:27])([F:26])[C:15]1[CH:24]=[C:23]2[C:18]([C@@H:19]([NH2:25])[CH2:20][CH2:21][O:22]2)=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.[N-:37]=[C:38]=[O:39].[Cl:40][C:41]1[CH:58]=[CH:57][C:44]([CH2:45][N:46]2[C:50]([C@H:51]3[CH2:55][CH2:54][CH2:53]N3)=[N:49][C:48]([CH3:56])=[N:47]2)=[CH:43][CH:42]=1>ClCCl>[Cl:40][C:41]1[CH:58]=[CH:57][C:44]([CH2:45][N:46]2[C:50]([C@H:51]3[CH2:55][CH2:54][CH2:53][N:37]3[C:38]([NH:25][C@@H:19]3[C:18]4[C:23](=[CH:24][C:15]([C:14]([F:13])([F:26])[F:27])=[CH:16][CH:17]=4)[O:22][CH2:21][CH2:20]3)=[O:39])=[N:49][C:48]([CH3:56])=[N:47]2)=[CH:43][CH:42]=1

참가 물질

7

반응물 5

HCID 81531Diisopropylethylamine2회HCID 94429TriphosgeneHCID 105034IsocyanateHCID 46911908(S)-7-(trifluoromethyl)chroman-4-amineHCID 57650059(R)-1-(4-chlorobenzyl)-3-methyl-5-(pyrrolidin-2-yl)-1H-1,2,4-triazole

생성물 1

HCID 57650243(R)-2-(2-(4-chlorobenzyl)-5-methyl-2H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl)pyrrolidine-1-carboxamide수율 15%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

To a stirring solution of triphosgene (18 mg, 0.06 mmol) in dichloromethane (3 ml) was slowly added dropwise via syringe a premixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (39 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.069 ml) dissolved in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 30 minutes. The isocyanate thereby generated was then treated dropwise with a solution of (R)-1-(4-chlorobenzyl)-3-methyl-5-(pyrrolidin-2-yl)-1H-1,2,4-triazole (52 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.067 ml, 0.4 mmol) dissolved in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated to dryness, diluted with EtOAc, washed with 5% aqueous NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. Purification by preparative HPLC yielded a clear oil (14 mg, 15%)

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 16 h
  2. customThe reaction mixture was evaporated to dryness
  3. additiondiluted with EtOAc
  4. washwashed with 5% aqueous NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by preparative HPLC

출처 및 근거

ORD 기록
ord-fb594d5674e549a188718983c11056d9
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288371B2

반응 노트

불러오는 중…